Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00352534

Purpose

RATIONALE: Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.

PURPOSE: This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor.

Condition	Intervention	Phase
Kidney Cancer	Biological: dactinomycin Drug: doxorubicin hydrochloride Drug: vincristine sulfate Procedure: conventional surgery Radiation: radiation therapy	Phase III

MedlinePlus related topics: Cancer Kidney Cancer Radiation Therapy Surgery Wilms' Tumor

Drug Information available for: Dactinomycin Vincristine Doxorubicin Doxorubicin hydrochloride Myocet Vincristine sulfate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Treatment for Very Low and Standard Risk Favorable Histology Wilms Tumor

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival at 4 years [ Designated as safety issue: No ]
Event-free survival at 4 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of contralateral kidney lesions in patients with very low-risk disease [ Designated as safety issue: No ]
Incidence of renal failure in patients with very low-risk disease [ Designated as safety issue: No ]

Estimated Enrollment:	600
Study Start Date:	October 2006
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Stratum I: Experimental (Very low-risk disease): Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.	Biological: dactinomycin Given IV Drug: doxorubicin hydrochloride Given IV Drug: vincristine sulfate Given IV Procedure: conventional surgery Patients undergo surgery Radiation: radiation therapy Patients undergo radiotherapy
Stratum II: Experimental (Standard-risk, stage I or II disease with adverse biological marker): Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.	Biological: dactinomycin Given IV Drug: doxorubicin hydrochloride Given IV Drug: vincristine sulfate Given IV Procedure: conventional surgery Patients undergo surgery
Stratum III: Experimental (Standard-risk, stage III disease): Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.	Biological: dactinomycin Given IV Drug: doxorubicin hydrochloride Given IV Drug: vincristine sulfate Given IV Procedure: conventional surgery Patients undergo surgery Radiation: radiation therapy Patients undergo radiotherapy

Detailed Description:

OBJECTIVES:

Primary

Evaluate the overall and event-free survival of younger patients with newly diagnosed stage I favorable histology Wilms' tumor (< 2 years of age and < 550gms) treated with nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin hydrochloride, and radiotherapy (standard risk).

Secondary

Determine the effects of adding doxorubicin hydrochloride to the regimen for patients with stage I or II favorable histology found to have a high-risk biological marker.
Determine whether the omission of adjuvant therapy increases the incidence of contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy and observation only.
Determine whether the omission of adjuvant therapy increases the incidence of renal failure in patients with very low-risk disease who have metachronous relapse.
Correlate study outcomes in patients with standard-risk disease with biological data from tissue collections on protocol study COG-AREN03B2.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical and biological risk factors (very low risk vs standard risk).

Stratum I (very low-risk disease): Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years.

Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy.

Treatment continues for up to 25 weeks.

Stratum II (standard-risk, stage I or II disease with adverse biological marker): Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.
Stratum III (standard-risk, stage III disease): Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks. After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 1,300 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 29 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed Wilms' tumor
- Newly diagnosed stage I-III disease
- Favorable histology
No moderate- or high-risk Wilms' predisposition syndromes
Must meet 1 of the following disease stratification categories:
- Very low-risk disease
  - Stage I disease
  - Age < 2 years
  - Tumor weight < 550 g
  - Regional lymph nodes histologically negative (must have been sampled)
  - No pulmonary metastases on CT scan of chest
- Standard-risk disease meeting 1 of the following criteria:
  - Disease does not require radiotherapy
    - LOH at chromosomes 1p and 16q for stage I or II
    - Stage I disease meeting 1 of the following criteria:
      - Age ≥ 2 years to age < 30 years
      - Tumor weight ≥ 500 g
    - Stage II disease
      - Age < 30 years
      - Any tumor weight
  - Disease requires radiotherapy
    - No LOH at chromosomes 1p and 16q*
    - Stage III disease NOTE: *Patients with combined loss of heterozygosity at chromosomes 1p and 16q will be eligible to transfer to protocol COG-AREN0533
Must be enrolled on protocol COG-AREN03B2

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 50-100% for patients > 16 years old
Lansky PS 50-100% for patients ≤ 16 years old
Bilirubin (direct) ≤ 1.5 times upper limit of normal (ULN)
AST or ALT < 2.5 times ULN
Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram (standard-risk disease)
Not pregnant or nursing
Negative pregnancy test
Fertile patient must use effective contraception

PRIOR CONCURRENT THERAPY:

No prior tumor-directed chemotherapy or radiotherapy
- Patients transferring from AREN03B2 with LOH 1p and 16q allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352534

Show 191 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Conrad V. Fernandez, MD, FRCPC	IWK Health Centre
Investigator:	Elizabeth A. Mullen, MD	Dana-Farber Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000487540, COG-AREN0532
Study First Received:	July 13, 2006
Last Updated:	May 7, 2009
ClinicalTrials.gov Identifier:	NCT00352534 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I Wilms tumor
stage II Wilms tumor
stage III Wilms tumor

Study placed in the following topic categories:

Urinary Tract Neoplasm
Kidney Cancer
Vincristine
Urogenital Neoplasms
Antimitotic Agents
Urologic Neoplasms
Doxorubicin
Carcinoma
Anti-Bacterial Agents
Renal Cancer
Neoplastic Syndromes, Hereditary
Urologic Diseases

Genetic Diseases, Inborn
Dactinomycin
Kidney Neoplasms
Wilms' Tumor
Tubulin Modulators
Carcinoma, Renal Cell
Wilms Tumor
Kidney Diseases
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Urogenital Neoplasms
Urologic Neoplasms
Antibiotics, Antineoplastic
Anti-Bacterial Agents
Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Dactinomycin
Therapeutic Uses
Wilms Tumor
Kidney Diseases
Nucleic Acid Synthesis Inhibitors

Neoplasms by Histologic Type
Mitosis Modulators
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Doxorubicin
Pharmacologic Actions
Carcinoma
Protein Synthesis Inhibitors
Neoplasms
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Tubulin Modulators
Carcinoma, Renal Cell
Adenocarcinoma

ClinicalTrials.gov processed this record on May 07, 2009